The objective of this proposal is to study the chemistry and biology of a newly discovered mitogenic growth factor polypeptide which is transported in human blood by platelets. This platelet-derived growth factor polypeptide (PDGF) has been recently purified to homogeneity. The specific activity of the purified PDGF is 20 million times greater than that found in unfractionated human serum. It stimulates replicative DNA synthesis and cell proliferation at concentrations of 0.1 nM. PDGF is heat-stable (100 degrees C) and has an isoelectric point of about 9.8. The unreduced molecule has a molecular weight of about 35,000 daltons as judged by SDS-PAGE. Reduction results in the production of two inactive polypeptide chains with molecular weights of about 13,000 and 17,000 respectively. PDGF is indispensable for the growth of normal connective tissue cells in culture. The specific aims include the elucidation of its primary structure using for this purpose highly sensitive protein sequenator procedures; investigation of the effect of selective chemical and enzymatic modification on its mitogenic activity and immunoreactivity with anti-PDGF antisera; application of a specific receptor binding assay for PDGF for the investigation of its molecular interaction with cells in culture, and the identification of the early events relevant to its function; and investigation of wheather or not human normal or malignant cells in culture produce a PDGF-like polypeptide. If such cell cultures are identified as producers, an effort will be made to arrest their growth with anti-PDGF anti-sera.